tbuckley/cabot-search huggingface dataset:
HER2-low expression as a prognostic factor in patients treated with CDK4/6 inhibitors: A retrospective analysis.
Authors: Mónica Cejuela Solís, Maria Angeles Castilla, Ana Gil, Alejandro Falcon, Marta Benavent, Isabel Miras Rodríguez, Manuel Ruiz-Borrego, Sonia Molina-Pinelo, Javier Salvador Bofill
Journal: Journal of Clinical Oncology (2023)

e13015 Background: Novel HER2 antibody-drug conjugates have demonstrated clinical benefit in breast cancer with HER2 IHC scores 1+ or 2+/ISH negative. As a result, a new concept of HER2 low breast cancer has been proposed. The prognostic implications of this expression remain unclear. To determine whether HER2 low expression affects disease evolution in patients with endocrine receptor positive, HER2 negative breast cancer, we performed a retrospective analysis of patients treated with first line CDK4/6 inhibitors in our center. Methods: We conducted a search for patients who received first line CDK4/6 inhibitors plus endocrine therapy at Virgen del Rocio Hospital between June 2016 and September 2021. 175 subjects were selected and followed for 42 months. Patients were grouped according to HER2 expression: HER2 0+ and HER2 low (IHC 1+ or 2+/ISH negative). Clinical characteristics and PFS were then compared. Clinical characteristics were evaluated by descriptive analysis. Kaplan Meier curves were used to estimate PFS, and Breslow test to estimate p-value. Statistical analyses were performed with SPSS 28.0. Results: All patients were female and median age at treatment initiation was 61 years. 49 patients received abemaciclib, 83 palbociclib and 43 ribociclib. 49 patients were HER2 0+, 57 HER2 1+ and 69 HER2 2+. Key clinical and treatment characteristics are shown. Overall PFS was 35.61 months (95% CI 25.46 - 45.76). PFS was 21.52 months (95% CI: 14.30 - 28.73), 31.15 months (95% CI: 15.59 - 46.70) and 39.49 months (95% CI: not estimable) in the HER2 0+, 1+ and 2+ population, respectively. There was no difference between the three arms: HER2 0+ vs HER2 1+ p=0.881; HER2 0+ vs HER2 2+ p=0.155; HER2 1+ vs HER2 2+ p=0.238. No significant differences were observed when comparing the HER2 0+ cohort to the overall HER2 low population: p=0.347. Conclusions: In our cohort of patients with luminal phenotype breast cancer treated with CDK4/6 inhibitors, HER2 low expression was associated with a trend toward longer PFS, although no statistically significant differences were found. [Table: see text]
Mutational landscape of intracranial germ cell tumors.
Authors: Jiangong Wang, Tiantian Han, Mengjuan Wang, Didi Guo, Rongrong Kong, Yuwei Dong, Ran Ding, Siqi Chen, Wanglong Deng, Fanfeng Bu
Journal: Journal of Clinical Oncology (2023)

e14060 Background: Intracranial germ cell tumours (GCTs) are relatively rare tumours of the central nervous system, which account for 1% to 3% of cases. The pathogenesis of intracranial GCTs is unknown, molecular diagnostic methods currently play only a minor role in the diagnosis of CNS germ cell tumours, which generally rest on histopathological and secretory features. The objective of this study was to explore the molecular profile associated with Chinese intracranial GCT patients. Methods: This study retrospectively analyzed the genomic features of 24 intracranial GCT patients. Next-generation sequencing (NGS) of 551-gene panel was performed to detect gene mutations in tumor and blood samples of the patients. Results: The tumors originated most frequently in the pineal region (41.6%, 10/24), followed by the sellar tumor (16.6%, 4/24). The average age of the patients was 14 years (range, 4-55years), There is a male preponderance of 2:1. The most common mutation genes were KIT (4.23%, n=6), KRAS (2.82%, n=4) and PTEN (2.11%, n=3). KIT mutations are mainly missense mutations concentrated in exon 17, exon 11 and exon 13. Exon 2 and exon 3 of KRAS gene were the main mutation hotspots, mainly G12X(2.08%) missense mutation. The co-mutation of KIT and KRAS was only in one patient. Unexpectedly, four patients (16.6%) carried germline deleterious mutations, in FANCA(n=1), FANCD2(n=1), FANCE(n=1), SDHA(n=1). Two of the patients with germline mutations co-mutated with KIT and KRAS, respectively. Conclusions: 16.6% of the intracranial GCT patients carry germline deleterious mutations, and 12.5% in Fanconi anemia (FA) gene. Overall, these findings indicate that the Fanconi anemia (FA) pathway and the PI3K/AKT pathway play a significant role in intracranial GCTs tumorigenesis.
Efficacy of adjuvant chemoradiotherapy in patients with pancreatic ductal adenocarcinoma after surgery: A real-world study in high-volume pancreatic cancer center.
Authors: Lili Wu, Xi Guo, Yaolin Xu, Dansong Wang, Wenchuan Wu, Tiantao Kuang, Xuefeng Xu, Liang Liu, Wenquan Wang, Shisuo Du, Yuhong Zhou, Wenhui Lou
Journal: Journal of Clinical Oncology (2023)

e16308 Background: Whether adjuvant chemoradiotherapy provides survival benefit for pancreatic ductal adenocarcinoma (PDAC) patients remains unknown. Methods: This prospective real-world study recruited PDAC patients receiving surgical treatment in Zhongshan Hospital Fudan University, Shanghai, China from June 2020 to December 2021. Patients with carcinoma in situ, distant metastases, synchronous cancers within 5 years, and receiving neoadjuvant therapy were excluded. Patients were then categorized into three groups according to their adjuvant treatment: C- (without adjuvant chemotherapy), C+R- (with adjuvant chemotherapy only), and C+R+ (with adjuvant chemoradiotherapy). Overall survival (OS) and disease free survival (DFS) were compared between groups. Results: A total of 216 patients were included in the final analyses. Median follow time for three groups ranged from 18 to 21.9 months. OS and DFS were significantly different between groups (OS, p value = 0.0088; DFS, p value = 0.0037). Median OS (mOS) for C- and C+R- were 24.3 (95% confidence interval [CI], 18 - not available [NA]) and 29.5 (24.9 – NA). Patients in C+R+ groups did not reach mOS (27.2 - NA). Median DFS (mDFS) for C-, C+R-, and C+R+ were 8.42 (5.72 - NA), 16.9 (13.91 - NA) and 19.66 (16.83 - NA), respectively. Conclusions: Adjuvant treatment significantly increased survival outcomes of pancreatic cancer patients after surgical treatment. In order to find out whom might benefit from additional radiotherapy and which is the best therapy combination, more detail information, including chemotherapy regimen, staging, resection margin, etc., were needed to include in the survival analyses. Clinical trial information: NCT04737551 . [Table: see text]
Efficacy and safety study of neoadjuvant efineptakin alfa (NT-I7) and pembrolizumab in recurrent glioblastoma.
Authors: Mason Webb, Terry C Burns, Erin Twohy, Ugur Sener, Sani Haider Kizilbash, Michael W. Ruff, Joon H. Uhm, Evanthia Galanis, Stacy D. D'Andre, Cecile Riviere-Cazaux, Byung Ha Lee, Lynn M. Flickinger, Ian F. Parney, Jian Li Campian
Journal: Journal of Clinical Oncology (2023)

TPS2085 Background: Glioblastoma (GBM) is the most common and aggressive form of brain tumor in adults. Despite maximal surgical resection, irradiation, and chemotherapy, median overall survival (OS) remains at only 30 weeks for recurrent GBM (rGBM) patients, emphasizing the need for novel treatments. GBM tumors are immunologically ‘cold,’ in that they have an immune-suppressive microenvironment with a low number of tumor-infiltrating lymphocytes (TIL). Interleukin 7 (IL-7) plays a key role in T cell development and survival. The physiological level of IL-7 increases to stimulate T cell expansion in lymphopenic condition. Previous studies have shown that lymphopenic GBM patients have shorter survival. However, their IL-7 levels are unexpectedly low. Efineptakin alfa (NT-I7), a long-acting IL-7, has been shown to increase effector CD8 T cells and reduce suppressor T-regulatory cells in murine GBM models, with subsequently improved OS. Further, we recently completed a Phase I study which showed that NT-I7 is safe, well- tolerated, and increased absolute lymphocyte counts (ALC) in newly diagnosed GBM patients. Phase II dosing was determined through this Phase I study reaching maximum tolerated dose. Thus, we hypothesized that NT-I7 may reverse GBM-associated immune suppression and potentiate the effect of an immune checkpoint inhibitor, leading to an increase in TILs and improved survival. Our preliminary data suggests that combining NT-I7 with pembrolizumab, an anti-PD-1 antibody, improves survival in murine glioma models. The purpose of this study is to evaluate the safety and efficacy of combining NT-I7 and pembrolizumab in rGBM patients. Methods: This is an open-label single arm one-stage Phase II study of NT-I7 and pembrolizumab as neoadjuvant and adjuvant therapy with surgery for adult patients with rGBM. We plan to enroll 30 evaluable patients, including a 6-patient safety run-in. Key eligibility criteria include candidates willing to undergo clinically indicated resection or biopsy, age ≥ 18 years, Karnofsky performance status ≥ 70, and dexamethasone dose &gt; 2 mg/day ≤ 2 days prior to registration. The primary endpoint is a 9-month OS rate. Secondary endpoints include progression-free survival, objective response rate, changes in ALC, and adverse events profile. The correlative endpoints include studies to assess the anti-glioma immune response, changes in T cell subsets, T cell effector function, cytokine analysis, and immunohistochemical analysis of GBM tissue. Longitudinal cerebrospinal fluid proteomics is optional. This study opened on 1/20/2023. Two of the planned 30 patients had been enrolled by submission on 2/14/2023. Clinical trial information: NCT05465954 .
Bioequivalence study of BH009 and Winthrop (docetaxel) injection (an authorized generic drug of Taxotere) in patients with advanced solid tumor: An open-label, randomized, single-dose, two-way crossover evaluation.
Authors: Qun Sun
Journal: Journal of Clinical Oncology (2023)

e13002 Background: Taxotere (docetaxel injection) clinically used to treat solid tumors (e.g., breast, prostate, gastric, lung, and head and neck cancer) is associated with hypersensitivity reactions attributed to its excipient, polysorbate 80. BH009 is a novel polysorbate 80-free formulation of docetaxel injection that could reduce hypersensitivity reactions associated with polysorbate 80 and preclude the need for dexamethasone premedication. Methods: This multicenter, randomized, open-label, two-way crossover study compared the pharmacokinetics and safety of BH009 and Taxotere (Winthrop (docetaxel) injection). Patients received single-dose of 75 mg/m 2 BH009 or Taxotere IV over 60 min, with ≥21-day washout between doses. Primary endpoints were to evaluate pharmacokinetics and establish the bioequivalence of BH009 relative to Taxotere. Blood samples were evaluated for pharmacokinetics and bioequivalence, and safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. A total of 46 subjects were randomized, and 41 subjects have completed the study. Results: The ratio of geometric means for AUC 0-t , AUC 0-∞ and C max following administration of BH009 (Test product (T)) and Taxotere (Winthrop (docetaxel) injection) (Reference product (R)), were 0.99 (90% CI, 91.89% - 107.18%) , 0.98 (90% CI, 91.10% - 106.04%) and 1.00 (90% CI, 92.18% - 108.00%), respectively. Statistical analyses reveal that 90% confidence interval for geometric least square mean ratio of (T/R) is within the acceptance range of 80.00% to 125.00% for primary pharmacokinetic parameters C max , AUC 0-t and AUC 0-∞ required for concluding bioequivalence between the test and reference product. The test and reference product were well tolerated by the patients, and the safety profile of the test product complies with the known safety profile of the reference product. A total of 198 TEAEs were reported during the course of the study. 94 TEAEs were reported after administration of Test product (T). 104 TEAEs were reported after administration of reference product (R). No serious adverse events or deaths occurred during the course of the study. Conclusions: This study established the bioequivalence of BH009 to Taxotere. BH009 is the first polysorbate 80-free formulation of docetaxel injection which is bioequivalent to Taxotere and may provide a safer alternative to Taxotere. Clinical trial information: NCT04889599 .
Identifying care fragmentation in the management of non-metastatic muscle-invasive bladder cancer.
Authors: Manisha Bhattacharya, Zhaojun Sun, Bruce Lee Jacobs, Jonathan G. Yabes, Lindsay M. Sabik
Journal: Journal of Clinical Oncology (2023)

e13527 Background: Measuring care fragmentation facilitates exploration of breakdowns in cancer care delivery that may impact quality of care and patient outcomes. Bladder cancer often requires a multimodal approach of surgery, chemotherapy and radiation, increasing the risk of fragmented care. This study assesses the extent of care fragmentation across different inpatient facilities and examines patient characteristics associated with inpatient care fragmentation. Methods: We adapt the modified Herfindahl-Hirschman market concentration index to construct a Fragmentation Index (FI) capturing the distribution of a patient’s care across inpatient facilities. We calculate FI for the 15 months following diagnosis for non-metastatic muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from 2010-2016 and had at least 2 admissions during the study period. We use Pennsylvania Cancer Registry data linked to statewide facility discharge records to estimate patient-level multivariable regression models of the relationship between FI and patient demographics, disease features, rurality, area deprivation index (ADI), payer, and Commission on Cancer hospital (CoC-H) accreditation status. Results: Of 965 patients, 87.3% (n = 842) lived in urban areas, 8.9% in large towns and 3.8% rural. Approximately 8% had Medicaid and 5.7% had uninsured or unknown payer status. A majority (64%; n = 614) were age 60-79; 76% were men and 92% non-Hispanic White; 19.5% (n = 188) had T4 disease and 25% (n = 239) received neoadjuvant chemotherapy. Almost half of patients (45.3%; n = 437) had an FI of 0, indicating all admissions were at the same hospital. The mean FI was 0.254 for the total cohort and 0.464 for patients with FI &gt; 0. Residency in a large town or rural area was associated with 0.59 (CI 0.003—0.114) and 0.14 (CI 0.060—0.220) higher FI relative to urban areas. T4 disease was associated with 0.063 higher FI (CI 0.019—0.107) relative to &lt;T2 disease. Factors associated with lower FI included Non-White race (-0.092, CI -0.151 – -0.033) and no admissions to CoC-H (-0.138, CI -0.182 – -0.095) relative to patients admitted to at least 1 CoC-H. Patients never admitted to a CoC-H (n = 134) mostly lived in urban areas (88%) and 49% had Medicare insurance: they were disproportionately from the most disadvantaged ADI quartile in the cohort (37.3%). Conclusions: Our findings highlight that many MIBC patients receive inpatient care across at least two different hospitals. Advanced disease and patient residence in non-urban areas are associated with greater fragmentation of inpatient care. Patients who never received care at a CoC hospital experienced less fragmentation but were more likely to be relatively economically disadvantaged. Future research will investigate relationships between fragmentation and clinical outcomes to inform policy and clinical strategies aimed at optimizing patterns of care.
International molecular tumour board: A transatlantic precision oncology collaboration.
Authors: David Gallagher, Emily O'Donovan, Elly Che Othman, Helen Sugrue, Lora Jane Black, Jenna Hove, Steven Francis Powell
Journal: Journal of Clinical Oncology (2023)

e13525 Background: Genomic testing (GT) is increasingly used to guide treatment in cancer care. There is considerable international variation in provider expertise and access to molecular tumor board (MTB) and therapeutics. In Ireland high quality GT is not broadly available; only 3% of patients receive treatment on a clinical trial. Our hypothesis is that increased GT would lead to enhanced treatment options and increase access to trials. Through institutional partnership between community cancer programs in Ireland and the United States (US), we offered GT and collaborative MTB review to patients with advanced cancer and observed the effect on treatment patterns. Methods: Eligible patients with metastatic solid tumors attending a single Irish community cancer unit between 2018 and 2022 were offered GT and collaborative MTB review on the COMPASS study. Testing was completed using a Foundation Medicine test reimbursed by multiple payors. Testing was performed on tumor tissue, or if not available, on circulating tumor DNA (ctDNA). Cases were presented virtually at MTB. Treatment decisions were based on MTB discussion of actionable alterations (AAs) with at least preclinical evidence of benefit, clinical trial availability, and local drug access. The primary outcome was impact of GT on treatment decision. Secondary outcomes included rate of AAs, and potential germline mutations. An exploratory objective evaluated potential matches to US-based NCI MATCH and ASCO TAPUR trials. Results: In total, 157 patients were screened and 120 enrolled on the COMPASS study. 46 (38.3%) male and 74 (61.7%) female with 25 different primary cancers. Tissue testing was performed for 79 (65.8%) patients and 35 (29.1%) had ctDNA testing. 105 (87.5%) patients had at least one AA by MTB criteria, 49 (46.7%) patients had more. Treatment decisions are outlined. 7 patients derived clinical benefit from treatment. 26 (21.7%) patients had a potential match for MATCH or TAPUR arms. MTB suggested 35 (29.1%) patients consider germline testing. 22 previously had genetic testing and 8 more had germline testing following GTB; 1 pathogenic germline mutation was identified. Conclusions: We successfully completely a transatlantic collaboration to introduce US MTB-directed care for Irish patients. The majority of patients had novel treatment options identified but drug access and clinical trial enrolment was limited by regional availability. International collaboration on precision oncology treatment trials should be prioritized.[Table: see text]
Health-related quality of life (HR-QOL) measures in renal cell carcinoma (RCC): Patient-reported relevance of items of the FKSI-19, EORTC QLQ-C30, and EQ-5D.
Authors: Cristiane Decat Bergerot, Benjamin D Mercier, Daniela V. Castro, Paulo Gustavo Bergerot, Charlotte Toms, Adil A Ali, Errol James Philip, Dr. Paulo Sergio Lages, Augusto C. A. Mota, Thomas E. Hutson, Viktor Grünwald, Axel Bex, Sarah P. Psutka, Brian I. Rini, Elizabeth R. Plimack, Viraj A. Master, Laurence Albiges, Toni K. Choueiri, Sumanta Kumar Pal, Thomas Powles
Journal: Journal of Clinical Oncology (2023)

4540 Background: Given the need to balance both quantity and quality of life among patients with advanced cancer, developing a robust, relevant, and consensus-driven patient-focused measurement strategy is a necessity. Our study expands upon previous findings (Bergerot et al., The Oncologist 2023) in evaluating the perceived relevance of questions on the FKSI-19, EORTC QLQ-C30, and EQ-5D among patients with RCC. Methods: Eligible patients were diagnosed with RCC and asked to evaluate the relevance of each question of the FKSI-19, EORTC QLQ-C30, and EQ-5D (items rated as relevant vs non-relevant). Patients also responded to 2 open-ended questions regarding topics not covered by these measures and their perception of wearable technologies. Questions identified as meaningful required ≥66% “relevant” ratings. Descriptive statistics were collated, and open-ended questions were analyzed by 2 independent reviewers (CB, PB). Results: 116 patients were recruited from Brazil and the US. Most (69%) were male with a median age of 64 (32-88) years. 83% were diagnosed with advanced disease, and 75% received immunotherapy and/or targeted therapy as primary treatment. Few items across surveys were identified as meaningful including 8/19 FKSI-19 questions (lack of energy, fatigue, appetite, sleeping, worry, able to work, enjoyment and quality of life), 3/30 EORTC QLQ-C30 questions (tired, overall health and quality of life), and 0/5 EQ-5D questions. Patients suggested items pertaining to treatment side effects, emotional symptoms, physical function, social/family support, and financial distress should be included. Notably, 58% of patients were open to using wearable devices to assess HRQOL. Conclusions: Our multi-institutional international study confirms findings from our single-institution pilot data suggesting that HRQOL measures for RCC require substantial refinement. These data will inform development of a novel-RCC specific HRQOL tool in a joint effort between experts and patients.
Exchanging genomics reports between pathology labs and medical centers using the Minimal Clinical Oncology Data Element (mCODE) FHIR implementation guide.
Authors: May Terry, Howard Anton, Michelle Casagni, Srikar Chamala, James Lin Chen
Journal: Journal of Clinical Oncology (2023)

e13575 Background: The automated transfer of discrete molecular data from pathology labs into the electronic health record (EHR) is rapidly becoming commonplace and is designed to facilitate clinical decision making. Simple genomic changes are represented in existing EHR data transfer standards, but current data standards lack clinical fields that correspond to treatment insights such as associated medications and potential clinical trials. To address this, the mCODE effort defines a consensus oncology data standard that facilitates lightweight transmission of data from patients with cancer. mCODE’s support of genomic data leverages efforts by the HL7 Clinical Genomics Working Group (HL7 CGWG) focusing on oncology. Here, we describe pilot efforts involving both a pathology partner and academic medical centers to extend mCODE FHIR (Fast Healthcare Interoperability Resources) implementation guide (IG) support of genomic data for data interchange and clinical decision support use cases. Methods: From 2021-2022, validation of the mCODE FHIR IG genomic data elements was performed in CodeX, a FHIR accelerator program. These elements encompassed: lab facility, test order information, pathologist, patient demographics, specimen, molecular studies and therapeutic implications. Genomic FHIR data elements were selected for their conciseness and clinical relevance for inclusion in the mCODE FHIR IG under the supervision of two oncology informaticians. As part of the mCODE FHIR IG pilot, synthetic solid tumor molecular patient reports were generated by Tempus Labs. These synthetic molecular reports were transformed into mCODE-conformant FHIR files for transfer. The mCODE IG can be found at http://hl7.org/fhir/us/mcode/ . Results: Over 50 Tempus data elements were analyzed and found to be readily mapped to mCODE genomics elements. Two categories of data elements required additional transformation: 1. Data elements requiring additional genomic database annotations; 2. FHIR syntax constraints like the concatenation of medications in the same drug class. The mCODE file was transmitted to Vanderbilt and the Children's Hospital LA from Tempus for decoding and downstream uses. This effort further informed the HL7 CGWG of needed IG clarifications for compatibility with other standardization efforts and genomic use cases. Conclusions: mCODE’s support of genomic data elements provides a lightweight genomics interchange standard compatible with an existing pathology lab report. Mapping from existing molecular pathology reports to mCODE required nominal alterations. Furthermore, mCODE’s alignment with HL7 genomics efforts ensure FHIR-based compatibility in other clinical domains and with developing international standards. Continued pathology lab and academic medical center collaboration is essential for mCODE refinement and adoption.